The authors of this manuscript have read the journal's policy and have the following competing interests: CHT, MEH, & JGM have received unrelated grant funding in the past from MedImmune in the previous 3 years. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.
Conceived and designed the experiments: CHT JDS JRCP KAR IML MEH JGM PAS. Performed the experiments: CHT JDS JRCP KAR YY PDM NK JB GL CAH CA IML MEH JGM PAS. Analyzed the data: CHT JDS JRCP PAS JGM MEH IML YY. Contributed reagents/materials/analysis tools: CHT JDS JRCP KAR PDM JBC RD JJ JS NK JB LLC BC GL CAH CA YY IML MEH JGM PAS. Wrote the paper: CHT JDS JRCP KAR PDM JBC RD JJ JS NK JB LLC BC GL CAH CA YY IML MEH JGM PAS.
¶ JGM and PAS are joint senior authors on this work.
School-located influenza vaccination (SLIV) programs can substantially enhance the sub-optimal coverage achieved under existing delivery strategies. Randomized SLIV trials have shown these programs reduce laboratory-confirmed influenza among both vaccinated and unvaccinated children. This work explores the effectiveness of a SLIV program in reducing the community risk of influenza and influenza-like illness (ILI) associated emergency care visits.
For the 2011/12 and 2012/13 influenza seasons, we estimated age-group specific attack rates (AR) for ILI from routine surveillance and census data. Age-group specific SLIV program effectiveness was estimated as one minus the AR ratio for Alachua County versus two comparison regions: the 12 county region surrounding Alachua County, and all non-Alachua counties in Florida.
Vaccination of ∼50% of 5–17 year-olds in Alachua reduced their risk of ILI-associated visits, compared to the rest of Florida, by 79% (95% confidence interval: 70, 85) in 2011/12 and 71% (63, 77) in 2012/13. The greatest indirect effectiveness was observed among 0–4 year-olds, reducing AR by 89% (84, 93) in 2011/12 and 84% (79, 88) in 2012/13. Among all non-school age residents, the estimated indirect effectiveness was 60% (54, 65) and 36% (31, 41) for 2011/12 and 2012/13. The overall effectiveness among all age-groups was 65% (61, 70) and 46% (42, 50) for 2011/12 and 2012/13.
Wider implementation of SLIV programs can significantly reduce the influenza-associated public health burden in communities.
Influenza is an important vaccine-preventable disease. Children demonstrate the highest levels of influenza transmission,
Three decades of computer modeling
The level of indirect effectiveness predicted by mathematical modeling investigations
In Florida (and elsewhere in the USA), the majority of routinely-administered vaccinations are funded through private health insurance. Children on Medicaid (a government-sponsored health care program for low income families) or who have no insurance are eligible to receive free vaccine through the Vaccines for Children Program (VFC) paid for by the US federal government. VFC recipients are required to obtain their vaccine at a local health department or specific VFC providers. Regardless of insurance status, most children who receive influenza vaccination do so at a health care facility.
Implementation of the Alachua County SLIV program is described in detail elsewhere.
Influenza vaccination rates for Alachua County were obtained from the Florida Department of Health's Florida SHOTS Vaccine Registry. Through collaboration between the Health Department and community pediatricians, all influenza vaccinations of Alachua County residents were entered into the Florida SHOTS Vaccine Registry. Because the state registry does not require all medical providers to report influenza vaccination, comparable vaccination coverage data were not available for other counties. However, we expect the vaccination coverage to be between 18%–31% among privately insured schoolchildren between 5–17 years old
Weekly influenza and influenza-like illness (ILI) associated outpatient visits to emergency departments and urgent care centers were obtained from Florida's Electronic Surveillance System for the Early Notification of Community-based Epidemics (ESSENCE). Emergency department and urgent care centers will be referred to as emergency care (EC). This system systematically downloads chief complaint data on a daily basis for all participating EC facilities within Florida. For the 2011/12 and 2012/13 school years, ESSENCE reporting covered approximately 79% of eligible facilities statewide, 65% in Region 3 (12 northeastern counties of the state, excluding Alachua County), and 100% in Alachua County (intervention); levels of participation by EC facilities before 2011 were not felt to be adequate to permit inclusion of ESSENCE data prior to 2011 in this study. The ESSENCE case definition for influenza and influenza like illness (ILI) is an outpatient visit to a reporting facility with a chief complaint of “influenza”, “flu”, or “fever” plus “cough” and/or “sore throat”. Investigators received the number of ILI-associated weekly visits aggregated by the patient's permanent county of residence and age-group (0–4, 5–17, 18–44, 45–64, and 65 years and older). County and age-group specific resident counts were obtained from the 2010 US Census,
To reduce the potential that ILI will be misclassified as being caused by influenza infection (
The proportion of the laboratory specimens positive for influenza A (light bar) and B (dark bar) viruses among isolates submitted by the states of the Health and Human Services Southeastern Health Region 4 to the National Respiratory and Enteric Virus Surveillance System maintained by the United States Centers for Disease Control and Prevention (CDC). Data are shown for 2011/12 and 2012/13.
The attack rates (AR) were estimated as the number of cases of ILI-associated emergency care visits per 100,000 resident population. ARs were estimated by epidemic period and age-group, for each of the following geographic regions: Alachua County; the 12 surrounding counties (Region 3); and all non-Alachua counties in Florida. The SLIV program effectiveness at reducing the risk of ILI-associated EC outpatient visits was estimated for each combination of epidemic period and age-group as one minus the ratio of the corresponding ARs for Alachua County and a comparison region (either Region 3 or Florida). The effectiveness among 5–17 year-olds is considered to estimate the overall protection, both direct and indirect, associated with the Alachua County SLIV program.
A sensitivity analysis was conducted to investigate potential bias due to differential levels of ascertainment of ILI-associated outpatient emergency care visits between Alachua County and the comparison areas. Since the number of ILI outpatient EC cases reported by ESSENCE facilities may be a function of the overall EC visit volume, the ARs for ILI-associated outpatient EC visits were standardized to the overall visit volume seen in Alachua County ESSENCE facilities. The existence of the SLIV program in Alachua County could plausibly exert influences on the sensitivity and/or the specificity of the county's ESSENCE system for ILI-associated outpatient EC visits, potentially through elevated vigilance by those responsible for reporting to ESSENCE. Any added vigilance among the surveillance staff at Alachua County ESSENCE facilities (relative to reporting ECs in the comparison areas) should be at least partially apparent in the rates of other chief complaints recorded by ESSENCE, even for chief complaints that are reasonably expected to be weakly associated or unassociated with the direct and/or indirect effects of the LAIV delivered by the SLIV program. The impact of this potential source of differential ascertainment was investigated by adjusting the point estimate for the SLIV program's effectiveness against ILI-associated outpatient EC visits using the estimate of the program's effect on each of three negative control outcomes (outpatient EC visits for gastrointestinal illness, respiratory illness other than ILI, or physical injury), as well as the combined effect on all three. A detailed description of the analytic approach for the sensitivity analysis is provided in
This research was reviewed and approved by the University of Florida Institutional Review Board. The aggregated data was anonymized and de-identified prior to analysis; therefore, informed consent was not required.
During the 2011/12 influenza season, approximately 47% of school-age (5–17 years) residents of Alachua County received influenza vaccination, with 10,490 students vaccinated with LAIV through the SLIV program and an additional 1,936 students receiving any type of vaccine from a non-SLIV source (
Age-Group | Vaccination Rate | Alachua County |
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School Year | 2006/07 | 2007/08 | 2008/09 | 2009/10 | 2010/11 | 2011/12 | 2012/13 | ||
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- | - | ||||||||
SLIV Program | 27% | - | - | 60% | 59% | 54% | 55% | ||
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SLIV Program | 24% | - | - | 40% | 36% | 36% | 40% | ||
- | - | - | |||||||
SLIV Program | - | - | - | - | 18% | 19% | 22% | ||
- | - |
The overall vaccination coverage levels for each age group includes all children vaccinated with at least one dose of the live attenuated influenza vaccine (LAIV) or inactivated influenza vaccine (IIV) received from the any provider. The SLIV program vaccination coverage level includes a subset of children vaccinated with LAIV through that program's activities. Vaccination coverage levels were based upon information recorded in the Florida SHOTS Vaccine Registry.
Denominator based on 2010 Census Data
Denominators based on student enrolment
The mild 2011/12 epidemic period
The weekly rate of ILI-associated outpatient EC visits per 100,000 population were consistently higher in the comparison regions (Region 3 and Florida) than in Alachua County (
Chief complaint information is reported for outpatient visits to 183 emergency departments and urgent care facilities located throughout the state of Florida. Rates are presented for Alachua County (bars), the location of a novel school-located influenza vaccination program, and two comparison regions: the nearby 12 counties (Region 3, dashed line) and all non-Alachua counties (Florida, solid line). The map inset depicts the locations of Alachua and Region 3 within the state of Florida.
SLIV Program Area | Comparison Areas | ||||||
Age-Group | Alachua County | All Non-Alachua Counties | Region 3 | ||||
Epidemic Period | 2011/12 | 2012/13 | 2011/12 | 2012/13 | 2011/12 | 2012/13 | |
(98, 239) | (244, 445) | (1,526, 1,573) | (2,179, 2,235) | (1,535, 1,677) | (2,018, 2,180) | ||
(64, 134) | (149, 248) | (466, 482) | (670, 689) | (533, 585) | (624, 680) | ||
(91, 128) | (276, 339) | (222, 229) | (433, 443) | (259, 284) | (490, 524) | ||
(41, 82) | (168, 242) | (86, 91) | (223, 232) | (75, 90) | (225, 251) | ||
(34, 94) | (146, 253) | (66, 71) | (222, 232) | (61, 80) | (177, 208) |
Due to the relative similarity between the age-group specific ARs for the Region 3 and Florida comparison regions (
School-age children (5–17 years) are the target age-group for the SLIV; thus, the SLIV effect in this age-group is considered a measure of the program's overall effectiveness. SLIV effects in all other age-groups are considered measures of indirect effectiveness. SLIV effectiveness is defined as 1 minus the ratio of the age-group specific seasonal attack rates for ILI-associated outpatient visits in Alachua County versus the rates for one of two comparison regions: the surrounding 12 counties (Region 3, open circles) and all non-Alachua counties of Florida (squares). Vertical error bars represent 95% confidence intervals.
Basis for Correction | All Non-Alachua Counties of Florida | Region 3 | ||||||||||
0–4 Years | 5–17 Years | 18–44 Years | 45–6 Years | ≥65 Years | All Ages | 0–4 Years | 5–17 Years | 18–44 Years | 45–64 Years | ≥65 Years | All Ages | |
83.5, 92.8 | 70.2, 85.3 | 42.4, 59.1 | 2.8, 50.0 | −50.3, 42.1 | 60.6, 69.5 | 84.0, 93.1 | 74.7, 87.5 | 52.0, 66.3 | −5.4, 47.0 | −49.2, 44.4 | 65.8, 73.6 | |
84.6, 94.0 | 72.5,87.3 | 35.0, 53.3 | 23.9, 61.9 | −3.5, 62.3 | 61.3, 70.6 | 81.8, 92.9 | 70.1, 86.4 | 27.0, 48.1 | −1.2, 48.9 | −23.8, 54.6 | 57.4, 66.9 | |
72.7, 89.2 | 57.4, 79.6 | 15.2, 40.3 | 5.8, 53.9 | −27.5, 52.1 | 44.8, 58.0 | 68.8, 87.9 | 55.7, 79.5 | 11.6, 39.2 | −22.5, 40.6 | −59.1, 39.4 | 40.6, 54.6 | |
77.2, 91.1 | 67.8, 85.4 | 29.5, 49.7 | 19.3, 59.5 | −19.5, 58.2 | 57.9, 67.5 | 77.9, 91.5 | 69.7, 86.4 | 21.2, 44.5 | −7.2, 46.1 | −49.4, 48.4 | 54.7, 65.0 | |
85.6, 94.5 | 70.1, 86.9 | 23.5, 45.4 | 11.0, 55.1 | −13.4, 58.5 | 54.4, 65.3 | 84.7, 94.2 | 71.2, 87.0 | 27.7, 48.9 | −1.1, 51.2 | −18.7, 56.9 | 57.1, 67.3 | |
79.6, 91.9 | 65.6, 84.1 | 23.2, 45.0 | 12.4, 56.2 | −20.5, 56.4 | 52.7, 63.8 | 78.4, 91.6 | 66.6, 84.8 | 20.4, 43.6 | −8.8, 45.3 | −40.4, 48.6 | 51.4, 62.7 |
Estimates of the effectiveness (%, bold font) of program toward reducing the number of cases for influenza-like illness associated outpatient visits to sentinel emergency departments and urgent care facilities (ECs), by comparison area, age-group, and correction factors. Ninety-five percent confidence limits are presented directly below each effectiveness estimate. With the exception of the unadjusted effectiveness, all estimates are standardized for differences between Alachua County and the comparison regions in the overall volume of outpatient EC visits (see text of
Basis for Correction | All Non-Alachua Counties of Florida | Region 3 | ||||||||||
0–4 Years | 5–17 Years | 18–44 Years | 45–64 Years | ≥65 Years | All Ages | 0–4 Years | 5–17 Years | 18–44 Years | 45–64 Years | ≥65 Years | All Ages | |
79.1, 88.3 | 62.5, 77.2 | 22.3, 36.7 | −8.1, 25.0 | −14.8, 33.1 | 41.8, 50.1 | 78.0, 87.8 | 60.8, 76.3 | 32.6, 45.6 | −4.1, 28.8 | −36.7, 22.1 | 44.2, 52.5 | |
81.0, 89.2 | 64.1, 78.1 | 12.6, 27.9 | 11.8, 40.5 | 15.7, 49.2 | 42.7, 51.8 | 74.2, 85.3 | 53.0, 71.2 | 1.0, 18.9 | −3.2, 32.1 | −21.5, 29.8 | 30.5, 40.8 | |
70.4, 83.3 | 46.3, 69.1 | −27.6, −1.1 | −14.2, 24.9 | −9.4, 35.8 | 14.4, 28.2 | 61.6, 77.7 | 33.3, 61.7 | −37.9, −7.8 | −31.2, 14.8 | −59.8, 7.6 | −0.6, 14.3 | |
− |
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69.0, 82.5 | 55.2, 73.5 | 6.9, 23.8 | 4.8, 37.3 | 5.1, 45.0 | 35.4, 45.9 | 66.3, 81.3 | 51.3, 70.5 | −3.6, 15.5 | −8.7, 28.2 | −33.4, 26.6 | 26.0, 37.6 | |
81.1, 89.6 | 60.4, 77.1 | −5.2, 15.0 | −3.7, 32.9 | 14.4, 50.2 | 32.0, 43.7 | 78.9, 88.1 | 56.7, 74.7 | −0.5, 20.8 | 0.7, 36.3 | −1.9, 41.3 | 31.9, 43.9 | |
74.5, 85.3 | 54.9, 72.8 | −7.1, 12.3 | −3.4, 30.8 | 4.3, 44.0 | 28.3, 39.7 | 70.3, 82.9 | 48.1, 69.1 | −11.6, 9.7 | −11.6, 27.0 | −29.1, 26.2 | 20.6, 32.6 |
Estimates of the effectiveness (%, bold font) of program toward reducing the number of cases for influenza-like illness associated outpatient visits to sentinel emergency departments and urgent care facilities (ECs), by comparison area, age-group, and correction factors. Ninety-five percent confidence limits are presented directly below each effectiveness estimate. With the exception of the unadjusted effectiveness, all estimates are standardized for differences between Alachua County and the comparison regions in the overall volume of outpatient EC visits (see text of
For both epidemic periods, indirect protection associated with the Alachua SLIV program decreased with increasing age (
As reflected in
During the 2011/12 and 2012/13 influenza epidemic period, a substantial reduction in the risk of ILI-associated outpatient EC visits among under 65 year-old residents of Alachua County was associated with vaccination of approximately 50% of all school-age children residing within the county through a routine school-located influenza vaccination program. The SLIV program is associated with a 70–79% reduction in the risk of medically-attended ILI among the 5–17 year-olds, a group with an overall vaccination coverage of 47–51%. The risk of ILI-associated outpatient EC visits among 0–4 year-old Alachua County residents was 84–89% lower than the rest of Florida, providing strong evidence that vaccination of school-aged children contributes indirect protection to younger members of the community.
We found some evidence of an indirect effect of the SLIV program among working-age adults (18–44 years), although the effect was relatively small after correction for overall EC visits volumes and/or the rates of presentation to reporting ECs for other negative control chief complaints. We would note, however, that the population in this age-group in Alachua County is highly atypical for Florida counties, including, as it does, approximately 50,000 students attending the University of Florida. These students constitute some 28% of the total population of the County, and have an immunization rate of <10%. Without this admixture of University students, who do not fit into the typical model of adults living at home with children, we wonder if the indirect vaccine effectiveness for the 18–44 year age-group may have been higher. The level of indirect effectiveness did continue to drop as we moved into older age-groups. This trend of decreased levels of indirect protection with increased age is consistent with higher vaccination coverage rates among older adults,
Similar to other studies,
Despite the ecologic nature of this study and its reliance on data collected by a surveillance system for clinical disease, the results of this study are consistent with smaller scale randomized trials and community-based studies. Our results among the 5–17 age-group are consistent with a study using PCR-confirmed influenza as the outcome, which saw a 60% reduction in risk of influenza in an elementary school with 50% of their students vaccinated with LAIV.
It is of interest that reductions in ILI rates in Alachua County were seen during both “epidemic” and “non-epidemic” time periods. Our initial concern was that this observation could be reflective of ascertainment or other bias in reporting of Alachua County cases through the ESSENCE system. However, despite an extensive sensitivity analysis we could not demonstrate the presence of any significant biases in relative levels of the ascertainment of ILI-associated outpatient EC visits for Alachua County versus the comparison regions, nor did we see any major biases in vaccine effectiveness rates for the 5–17 and 0–4 year age-groups. Because of concerns that these corrections might, in and of themselves, inadvertently introduce additional biases, we elected to present the uncorrected values in the main body of the manuscript. Further discussion of the potential implications of the bias studies is provided in the
In considering possible reasons for the non-negligible summer ILI rates: Alachua County has had an aggressive SLIV program since the fall of 2009, with overall immunization rates among schoolchildren consistently above 40%. It may be that maintenance of consistently high levels of immunity in a community among the age-group associated with elevated influenza transmission,
Our results show that immunization of school-age children with influenza vaccination protects them from ILI-associated outpatient EC visits, and also protects the very young, one of the most vulnerable age-groups for adverse morbidity and mortality outcomes.
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We are grateful to all Alachua SLIV team members (school nurses, school and health department personnel, University of Florida faculty/staff, program assistants/coordinators, interns, and volunteers) for their dedication and enthusiasm. We recognize Tom Belcuore, Dan Boyd, and Robert Walker for jump starting this project in 2006/07. Other individuals we are grateful for are Jean Munden, Josephine McElrath, Patricia Hughes, Mimosa McNerney, Channing McArthur, Natalie Small, Kathy Black, Carl Pearson, Ian Kracalik, Mary Peoples-Sheps, David Atrubin, and others for support.
We thank the residents of Alachua County, the Alachua County Health Department, the Alachua County public and private schools, and the county pediatricians for building the foundation of this school-located influenza vaccination (SLIV) program. Additionally, we want to recognize the Alachua County commissioners, and the Gainesville City commissioners, the School Board of Alachua County, the other 29 community organizations/businesses (Medical Reserve Corps, AvMed Health Care, Choices Health Services, Sweet Dreams Ice Cream Shop, United Way of North Central Florida, Alachua County Public Health Foundation, African American Accountability Alliance, Black Nurses Association, Children's Miracle Network, Crevasse's Regency Florist, Emerging Pathogens Institute, Gainesville Area Chamber of Commerce, Gainesville Health and Fitness, Gator Domino's, Junior League of Gainesville, Krispy Kreme Doughnuts, Marketing Mud, Publix, Renaissance Printing, Santa Fe College of Nursing Program, Texas Roadhouse, The Oaks Mall, TNT Graphics, Office Depot, UF College of Medicine, UF College of Nursing, UF College of Pharmacy, UF College of Public Health and Health Professions, UF Department of Pediatrics, and Walmart), and others we may have missed for supporting the Alachua SLIV program's mission of protecting the community from influenza by vaccinating schoolchildren.